Hydroxystilbene/ascorbic acid compositions for treating skin afflictions

ABSTRACT

Cosmetic/dermatological compositions, well suited, e.g., for skin-firming and anti-aging applications, as well as for stimulating the proliferation of dermal fibroblasts, comprise effective skin affliction-alleviating amounts of (a) at least one hydroxystilbene compound, in immixture with (b) at least one ascorbic acid compound, advantageously formulated into a topically applicable, physiologically/cosmetically acceptable vehicle, diluent or carrier therefor.

CROSS-REFERENCE TO PRIORITY APPLICATION

[0001] This application claims priority under 35 U.S.C. §119 ofFR-9908570, filed Jul. 2, 1999, hereby expressly incorporated byreference.

BACKGROUND OF THE INVENTION

[0002] 1. Technical Field of the Invention

[0003] The present invention relates to novel cosmetic/dermatologicalcompositions comprising at least one hydroxystilbene in intimateadmixture with ascorbic acid, especially for skin-firming applications.

[0004] In particular, the novel compositions of this invention are wellsuited to stimulate the restructuring of the skin and/or mucousmembranes by stimulating the proliferation of the dermal fibroblasts.

[0005] 2. Description of the Prior Art

[0006] Human skin includes two compartments or constituents, i.e., asuperficial compartment, the epidermis, and a deep compartment, thedermis.

[0007] Natural human skin is principally composed of three types ofcell: the keratinocytes, which are the vast majority, the melanocytesand the Langerhans cells. Each of these cell types contributes, byvirtue of its intrinsic functions, towards the essential role played inthe body by the skin.

[0008] The dermis provides the epidermis with a soft support. It is alsothe epidermis' nourishing factor. It primarily includes fibroblasts andan extracellular matrix itself composed of different extracellularproteins, among which are, in particular, collagen, elastin and variousglycoproteins. This assembly of extracellular components is synthesizedby the fibroblasts. Leukocytes, mastocytes and tissue macrophages arealso found in the dermis. Too, the dermis contains blood vessels andnerve fibers.

[0009] On account of their activity in the synthesis of theextracellular matrix proteins (proteoglycans, collagen fibers and otherstructural glycoproteins), the fibroblasts are the principal factorsinvolved in the structural development of the dermis.

[0010] The collagen fibers provide the dermis with solidity. They arevery strong, but are sensitive to certain enzymes generally referred toas collagenases. In the dermis, the collagen fibers comprise fibrilssealed together, thus forming more than ten different types ofstructure. The structure of the dermis is essentially due to theoverlapping of the trapped collagen fibers. The collagen fiberscontribute to the skin's tonicity. The collagen fibers are regularlyrenewed, but this renewal decreases with age, thus leading, especially,to a thinning of the dermis. This thinning of the dermis is also due topathological causes such as, for example, the hypersecretion ofcorticoid hormones, certain diseases (Marfan's syndrome, Ehlers-Danlossyndrome) or vitamin deficiencies (scurvy). It is also accepted thatextrinsic factors such as ultraviolet radiation, tobacco or certaintreatments (retinoic acid and derivatives, glucocorticoids, vitamin Dand derivatives, for example) also have an effect on the skin and on itscollagen level.

[0011] Degradation of the collagen fibers results, notably, in theappearance of loose, wrinkled skin which individuals have always triedto combat, since skin which looks smooth and taut is obviously morepreferred.

[0012] Moreover, during menopause, the principal changes relating to thedermis are a decrease in the level of collagen and in the thickness ofthe dermis. In menopausal women, this results in thinning of the skin.Women thus experience a sensation of “dry skin” or of skin which feelstight, and an increase in the level of surface wrinkles and fine linesdeveloped. The skin feels rough to the touch. Lastly, the skin is lesssupple. It is demonstrated that women gradually lose their level ofcollagen yearly after menopause and that 30% of the overall level islost in the first five years after menopause.

[0013] Thus, serious need continues to exist for alternative activeagents that maintain the level of collagen in the skin and also maintainthe smooth and taut appearance of the skin.

[0014] One approach for achieving this result entails stimulating theproliferation of the fibroblasts and, consequently, on account of theincrease in the number of secretory cells in the dermis, alsomaintaining or even reinforcing/enhancing the synthesis of collagen.

SUMMARY OF THE INVENTION

[0015] It has now surprisingly and unexpectedly been determined thatassociation of at least one hydroxystilbene with ascorbic acid or one ofthe analogs thereof presents the attribute of stimulating theproliferation of the dermal fibroblasts in proportions that are higherthan those which would reasonably be expected by simple addition of theeffects of each of these components taken separately.

DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OFTHE INVENTION

[0016] More particularly according to the present invention, the subjecthydroxystilbenes are compounds having the following structural formula(I):

[0017] in which n is an integer ranging from 0 to 4, inclusive, and m isan integer ranging from 0 to 5, inclusive.

[0018] These compounds can be in cis- or trans-configuration.

[0019] According to this invention, by the term “hydroxystilbene” areintended both the compounds of formula I and the hydroxyalkylderivatives thereof.

[0020] The hydroxystilbenes are compounds that exist in the naturalstate in plants of the Spermatophyte class and particularly in vine.Such compounds as, for example, resveratrol are found in grapes and inwine.

[0021] In the prior art, the hydroxystilbenes are useful, inter alia, asdepigmenting agents (JP-87192,040), as vasodilators (EP-96830,517), asantithrombin agents (JP-05016,413), for the treatment of variouscardiovascular conditions (CA-2,187,990), as mutagenesis andcarcinogenesis inhibitors (JP-06/24,967) or are described asantioxidants.

[0022] Among these compounds, resveratrol (or 3,5,4′-trihydroxystilbene)is particularly interesting for the activities described above, notablybecause it is a natural compound which is found in the skin ofgrapeseeds and in wine. In this regard, the review by Soleas et al.(Clinical Biochemistry, Vol. 30, No. 2, pp. 91-113 (1997)) wellsummarizes the state of the art regarding this compound andhydroxystilbenes.

[0023] Moreover, ascorbic acid (or vitamin C) is known to stimulatecollagen synthesis by preventing, as a co-factor, the self-inactivationof the lysine and proline hydroxylase enzymes and by increasing thesynthesis of procollagen mRNAs. Ascorbic acid (or vitamin C) is alsoknown to stimulate the synthesis of elastin in the skin. In this regard,compare U.S. Pat. Nos. 5,801,192 and 4,983,382 and EP-0,717,983. See,also the article entitled “Pola to incorporate vitamin C in newcosmetics line for skin care” from the Japan Economic Journal of Jun. 5,1984 (page 15). Thus, it has been described that ascorbic acid incosmetic compositions is useful for treating wrinkles (FragranceJournal, Vol. 8, No. 6(45) (1980) pp. 38-43, “Cosmetic and vitaminaction and safety to dermatology”).

[0024] Thus, the present invention features compositions comprising, ina physiologically acceptable medium, at least one hydroxystilbene inimmixture with ascorbic acid or with an analog thereof.

[0025] The subject compositions are particularly suited for stimulatingthe proliferation of dermal fibroblasts.

[0026] Exemplary hydroxystilbenes according to this invention are mono-,di-, tri-, tetra-, penta-, hexa-, hepta-, octa- andnonahydroxystilbenes, or, alternatively, hydroxyalkyl derivativesthereof.

[0027] According to the invention, the hydroxystilbenes can be usedalone or as mixtures of any nature and can be of natural or syntheticorigin.

[0028] The hydroxystilbenes according to the invention are preferablyselected from among:

[0029] 4′-hydroxystilbene,

[0030] 2′,4′-dihydroxystilbene,

[0031] 3′,4′-dihydroxystilbene,

[0032] 4,4′-dihydroxystilbene,

[0033] 2′,4′,4-trihydroxystilbene,

[0034] 3′,4′,4-trihydroxystilbene,

[0035] 2,4,4′-trihydroxystilbene,

[0036] 3,4,4′-trihydroxystilbene,

[0037] 3,4′,5-trihydroxystilbene,

[0038] 2′, 3,4-trihydroxystilbene,

[0039] 2,3′, 4-trihydroxystilbene,

[0040] 2′,2,4′-trihydroxystilbene,

[0041] 2,4,4′, 5-tetrahydroxystilbene,

[0042] 2′,3,4′,5-tetrahydroxystilbene,

[0043] 2,2′, 4,4′-tetrahydroxystilbene,

[0044] 3,3′, 4′,5-tetrahydroxystilbene,

[0045] 2,3′, 4,4′-tetrahydroxystilbene,

[0046] 3,3′,4,4′-tetrahydroxystilbene,

[0047] 3,3′,4′,5,5′-pentahydroxystilbene,

[0048] 2,2′, 4,4′,6-pentahydroxystilbene,

[0049] 2,3′, 4,4′,6-pentahydroxystilbene,

[0050] 2,2′, 4,4′,6,6′-hexahydroxystilbene.

[0051] 3,4′,5-Trihydroxystilbene, or resveratrol, is the preferredcompound according to the invention.

[0052] The ascorbic acid analogs are more particularly the saltsthereof, especially sodium ascorbate, magnesium or sodium ascorbylphosphate, the esters thereof, especially the acetic, propionic,palmitic, cinnamic or ferulic esters thereof, or the sugars thereof,especially glycosylated ascorbic acid. Thus, by the term “ascorbic acidcompound” are intended ascorbic acid itself, as well as the analogsthereof

[0053] The ascorbic acid is typically in L-configuration, since it isusually extracted from natural products.

[0054] According to the invention, the ascorbic acid and/or the analogsthereof can be used alone or as mixtures of any nature and can be ofnatural or synthetic origin.

[0055] The compositions of the invention are particularly useful fortopical application onto the skin and/or mucous membranes.

[0056] As indicated above, collagen is involved in the solidity of thedermis, and thus in the firmness of the skin and/or mucous membranes.Also, the fibroblasts are responsible for the synthesis of the proteinsof the extracellular dermal matrix, in particular of collagen.

[0057] Thus, the present invention features compositions comprising atleast one hydroxystilbene in admixture with ascorbic acid, suchcompositions being well suited to preventively or curatively treat thesigns of aging of the skin, more particularly to preventively orcuratively treat or combat loose and/or wrinkled skin.

[0058] The subject compositions are especially well suited to reduce thesigns of aging of the skin, more particularly to reduce the appearanceof loose and/or wrinkled skin.

[0059] The present invention also features compositions comprising atleast one hydroxystilbene in combination with ascorbic acid or analogthereof, for stimulating firming of the skin.

[0060] Too, this invention features compositions comprising at least onehydroxystilbene in combination with ascorbic acid or an analog thereof,for promoting the smoothness of the skin and/or to make the skin taut.

[0061] In another embodiment of the invention, compositions comprisingat least one hydroxystilbene in combination with ascorbic acid or ananalog thereof are used to combat the effects of menopause on the skin,more particularly the effects of menopause on collagen and/orfibroblasts.

[0062] The amounts of hydroxystilbene and of ascorbic acid or analogsthereof which are administered according to the invention obviouslydepend on the desired effect.

[0063] For example, the amount by weight of hydroxystilbene which can beadministered according to the invention advantageously ranges, forexample, from 0.001% to 10% and preferably from 0.005% to 5% relative tothe total weight of the composition.

[0064] To provide an order of magnitude, the amount by weight ofascorbic acid or of analogs thereof which is administered according tothe invention advantageously represents from 0.001% to 20% relative tothe total weight of the composition, preferably from 0.1% to 15%relative to the total weight of the composition and, moreadvantageously, from 3% to 10% relative to the total weight of thecomposition.

[0065] In the compositions of the invention, the weight ratio betweenthe hydroxystilbene and the ascorbic acid advantageously ranges from5'10⁻⁵ to 10⁺⁴ and preferably from 10⁻³ to 2.

[0066] In addition, the compositions of the invention are administeredfor a period of time which is sufficient to elicit the expected results.To provide an order of magnitude, this period of time can be a minimumof 3 weeks, but can also be more than 4 weeks, or even more than 8weeks.

[0067] The subject compositions are preferably intended for cosmetic ordermatological usage, advantageously cosmetic use.

[0068] The compositions of the invention for topical application containa physiologically acceptable medium, i.e., a medium which is compatiblewith the skin, including the scalp, mucous membranes and/or the eyes,and can especially constitute a cosmetic or dermatological composition.

[0069] The present invention the combination of at least onehydroxystilbene and of ascorbic acid or an analog thereof, topreventively or curatively treat the signs of aging of the skin, moreparticularly to preventively or curatively treat loose and/or wrinkledskin.

[0070] The subject compositions are preferably well suited to reduce thesigns of aging of the skin, more particularly to reduce the appearanceof loose and/or wrinkled skin.

[0071] This invention also features the combination of at least onehydroxystilbene and ascorbic acid or analog thereof for skin-firmingapplications.

[0072] Thus, this invention features the combination of at least onehydroxystilbene and of ascorbic acid or an analog thereof for smoothingthe skin or making it taut.

[0073] Too, the present invention features compositions comprising atleast one hydroxystilbene and ascorbic acid or analog thereof tostimulate the proliferation of dermal fibroblasts.

[0074] Lastly, the present invention features compositions comprising atleast one hydroxystilbene and ascorbic acid or analog thereof, to combatthe effects of menopause on the skin, more particularly the effects ofmenopause on the fibroblasts.

[0075] It will be appreciated that the compositions according to theinvention comprise a cosmetically acceptable support (vehicle, diluentor carrier) i.e., a support which is compatible with the skin, mucousmembranes, the nails and the hair, and can be in any pharmaceutical formnormally used for topical application, in particular in the form of anaqueous, aqueous/alcoholic or oily solution, an oil-in-water orwater-in-oil or multiple emulsion, an aqueous or oily gel, a liquid,pasty or solid anhydrous product, a dispersion of oil in an aqueousphase with the aid of spherules, it being possible for these spherulesto be polymer nanoparticles such as nanospheres and nanocapsules or morepreferably lipid vesicles of ionic and/or nonionic type.

[0076] The subject compositions can be more or less fluid and can beformulated as a white or colored cream, an ointment, a milk, a lotion, aserum, a gel, a paste or a mousse. They can optionally be applied to theskin in the form of an aerosol. They can also be in solid form, and, forexample, be in the form of a tube or stick. They can be used as a careproduct, as a cleansing product, as a makeup product or as a simpledeodorant product.

[0077] In known fashion, the compositions according to the invention canalso contain adjuvants and additives that are common in cosmetics anddermatology, such as hydrophilic or lipophilic gelling agents,hydrophilic or lipophilic active agents, preservatives, antioxidants,solvents, fragrances, fillers, screening agents, pigments, chelatingagents, odor absorbers, dyestuffs and colorants. The amounts of thesevarious adjuvants and additives are those used conventionally in thefields under consideration, and, for example, constitute from 0.01% to20% relative to the total weight of the composition. Depending on theirnature, these adjuvants and additives can be formulated into the fattyphase, into the aqueous phase, into the lipid vesicles and/or into thenanoparticles.

[0078] When a composition of the invention is an emulsion, theproportion of the fatty phase advantageously ranges from 5% to 80% byweight, and preferably from 5% to 50%, relative to the total weight ofthe composition. The oils, the emulsifiers and the co-emulsifiersformulated into the composition in emulsion form are selected from amongthose conventional in the fields under consideration. The emulsifier andthe co-emulsifier are typically present in the compositions in aproportion ranging from 0.3% to 30% by weight, and preferably from 0.5%to 20%, relative to the total weight of the composition.

[0079] Exemplary oils which can be formulated into the composition ofthe invention, include mineral oils, oils of plant origin (apricot oil,sunflower oil), oils of animal origin, synthetic oils, silicone oils andfluoro oils (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fattyacids and waxes (beeswax) can also be used as fatty substances.

[0080] Exemplary emulsifiers and co-emulsifiers include, for example,fatty acid esters of polyethylene glycol, such as PEG-40 stearate andPEG-100 stearate, and fatty acid esters of polyols, such as glycerylstearate and sorbitan tristearate.

[0081] And exemplary hydrophilic gelling agents include in particular,carboxyvinyl polymers (carbomer), acrylic copolymers such asacrylatealkylacrylate copolymers, polyacrylamides, polysaccharides,natural gums and clays, and exemplary lipophilic gelling agents includethe modified clays such as bentones, metal salts of fatty acids,hydrophobic silica and polyethylenes.

[0082] The subject compositions can contain other hydrophilic activeagents such as proteins or protein hydrolysates, amino acids, polyols,urea, allantoin, sugars and sugar derivatives, water-soluble vitamins,plant extracts and hydroxy acids.

[0083] Retinol (vitamin A) and derivatives thereof, tocopherol (vitaminE) and derivatives thereof, essential fatty acids, ceramides, essentialoils and salicylic acid and derivatives thereof are representativelipophilic active agents.

[0084] According to the invention, in combination with thehydroxystilbene can be associated compounds selected from among:

[0085] (1) plant hormones;

[0086] (2) calcium antagonists such as verapamil and diltiazem;

[0087] (3) OH radical scavengers such as dimethyl sulfoxide;

[0088] (4) chlorine-channel openers

[0089] (5) plant extracts such as those from Iridaceae, from Rosaceae orfrom soybean, these extracts also possibly containing isoflavones;

[0090] (6) extracts from microorganisms including, in particular,bacterial extracts such as those from non-photosynthetic filamentousbacteria.

[0091] Other compounds are also intended, namely, for example,potassium-channel openers such as diazoxide and minoxidil, spiroxazone,phospholipids such as lecithin, linoleic and linolenic acids, salicylicacid and derivatives thereof described in FR-2,581,542, such assalicylic acid derivatives bearing an alkyl group containing from 2 to12 carbon atoms in position 5 of the benzene ring, hydroxycarboxylic orketocarboxylic acids and their esters, lactones and their correspondingsalts, anthralin, carotenoids, eicosatetraenoic and eicosatrienoic acidsor the esters and amides thereof, and vitamin D and derivatives thereof.

[0092] According to the invention, it is also intended, inter alia, tocombine the at least one hydroxystilbene with other active agentssuited, in particular, for preventing and/or treating a variety of skinconditions. Exemplary such active agents include:

[0093] (a) agents which modify skin differentiation and/or proliferationand/or pigmentation, such as retinoic acid and its isomers, retinol andits esters, vitamin D and derivatives thereof, estrogens such asestradiol, kojic acid or hydroquinone;

[0094] (b) antibacterial agents such as clindamycin phosphate,erythromycin or antibiotics of the tetracycline class;

[0095] (c) agents which modify the adhesion of bacteria to the skinand/or to mucous membranes, such as honey, in particular acacia honeyand certain sugar derivatives;

[0096] (d) antiparasitic agents, in particular metronidazole, crotamitonor pyrethroids;

[0097] (e) antifungal agents, in particular compounds of the imidazoleclass such as econazole, ketoconazole or miconazole or their salts,polyene compounds such as amphotericin B, compounds of the allylaminefamily such as terbinafine, or octopirox;

[0098] (f) antiviral agents such as acyclovir;

[0099] (g) steroidal anti-inflammatory agents such as hydrocortisone,betamethasone valerate or clobetasol propionate, or nonsteroidalanti-inflammatory agents such as ibuprofen and its salts, diclofenac andits salts, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid;

[0100] (h) anaesthetics such as lidocaine hydrochloride and derivativesthereof;

[0101] (i) anti-pruriginous agents such as thenaldine, trimeprazine orcyproheptadine;

[0102] (j) keratolytic agents such as α- and β-hydroxycarboxylic orβ-ketocarboxylic acids, their salts, amides or esters, and moreparticularly hydroxy acids such as glycolic acid, lactic acid, salicylicacid, citric acid and fruit acids in general, and 5-n-octanoylsalicylicacid;

[0103] (k) anti-free-radical agents such as α-tocopherol or its esters,superoxide dimutases, certain metal-chelating agents or ascorbic acidand its esters;

[0104] (l) anti-seborrhoeic agents such as progesterone;

[0105] (m) antidandruff agents such as octopirox or zinc pyrithione;

[0106] (n) anti-acne agents such as retinoic acid or benzoyl peroxide;

[0107] (o) substances such as antagonists of substance P, of CGRP or ofbradykinin or NO synthase inhibitors or alternatively sodium-channelinhibitors, compounds described as being active in the treatment ofsensitive skin and as having anti-irritant effects, in particular withrespect to irritant compounds which may be present in the compositions.

[0108] Moisturizers such as polyols (for example glycerol), vitamins(for example D-panthenol), anti-inflammatory agents, calmatives(allantoin, cornflower water), UVA and UVB screening agents, matt-effectagents (for example the partially crosslinkedpolydimethylorganosiloxanes marketed under the trademark KSG® by ShinEtsu), and mixtures thereof are particularly useful active agents.

[0109] Anti-wrinkle active agents, and in particular tautening productssuch as plant proteins and their hydrolysates, in particular the soybeanprotein extract marketed under the trademark Eleseryl® by LSN or the oatderivative marketed under the trademark Reductine® by Silab, can also beadded.

[0110] Since the skin comprises many more components or constituentsthan just collagen and fibroblasts, it is found to be advantageous, whena combination of hydroxystilbene and ascorbic acid is used according tothe invention, to simultaneously promote the synthesis of these othercomponents, for example such as the lipids, and/or to promote theproliferation of other cell components, for example the keratinocytes.

[0111] Thus, this invention features cosmetic compositions comprising,in a cosmetically acceptable medium, a combination of at least onehydroxystilbene and of ascorbic acid or an analog thereof and at leastone other active species for stimulating the synthesis of lipids and/orthe proliferation of keratinocytes.

[0112] In this regard, active species for stimulating the synthesis oflipids which are exemplary are plant hormones, such as auxins, orcompounds of plant origin, such as cinnamic acid, and products forstimulating the proliferation of keratinocytes which are exemplary arecompounds of plant origin, such as phloroglucinol.

[0113] Thus, in addition to hydroxystilbene and ascorbic acid, thecompositions according to the invention can comprise cinnamic acid orderivatives thereof and/or a plant hormone, particularly an auxinselected from among indoleacetic acid (IAA), 4-chloroindole-3-aceticacid (4-Cl-IAA), phenylacetic acid (PAA), indole-3-butyric acid (IBA),2,4-dichlorophenoxyacetic acid (2,4-D), α-naphthaleneacetic acid(α-NAA), β-naphthoxyacetic acid, indolethanol, indoleacetaldehyde andindoleacetonitrile and/or a plant compound such as phloroglucinol.

[0114] In order to further illustrate the present invention and theadvantages thereof, the following specific examples are given, it beingunderstood that same are intended only as illustrative and in nowiselimitative.

[0115] In said examples to follow, all parts and percentages are givenby weight, unless otherwise indicated.

EXAMPLE 1 Study of the effect of resveratrol on the proliferation ofdermal fibroblasts

[0116] The study has carried out by measuring the incorporation ofradioactive thymidine into normal human dermal fibroblast cultures.

[0117] The fibroblast cultures were prepared according to the standardmethods of cell culturing, i.e., in MEM/M199 medium marketed by Gibco,in the presence of sodium bicarbonate (1.87 mg/ml), L-glutamine (2 mM),penicillin (50 IU/ml) and 10% foetal calf serum (Gibco).

[0118] The test was carried out on cell cultures at 80% of confluence on24-well plates. Resveratrol, at a concentration of 1.25 μM and 5 μM, wasplaced in contact with the cells for 48 hours. Labeling with tritiatedthymidine ([methyl-3H] thymidine marketed by Amersham, 82 Ci/mmol) wascarried out for 24 hours.

[0119] The level of tritiated thymidine incorporated was measured at theend of the test by acidic precipitation of the proteins on filters andcounting by liquid scintillation.

[0120] The results were evaluated relative to a control consisting ofcells which had not been treated.

[0121] A positive control [EGF : Epidermal Growth Factor] at 1.67×10⁻³μM, which was known to stimulate fibroblast proliferation, wasintroduced into the test by way of reference.

[0122] The results of this test are reported in the Table below: TABLETreatment cpm s.d. % p Untreated 10320 1427 100 — EGF (1.67 × 10⁻³ μM)29214 1825  283 (+183) <0.001 (+18894) 20 μm vitamin C 13595 1394 132(+32) <0.05  (+3275) 5.00 μM 11365 613 110 (+10) >0.05 resveratrol (+1045) 5 μM resveratrol + 18944 331 184 (+84) <0.001 20 μM vitamin C (+8624)

[0123] The results reported in the table above unambiguously evidencethat the resveratrol/vitamin C combination synergistically stimulatedfibroblast proliferation markedly more than would have been predicted byadding the effects measured for resveratrol and vitamin C usedindividually. A synergistic effect between resveratrol and vitamin C onfibroblast proliferation exists when the two products are usedsimultaneously.

EXAMPLE 2

[0124] The following are specific examples of formulations according tothe invention.

[0125] These compositions were formulated according to typicalcosmetic/pharmacy techniques. Composition 1: Care cream beeswax 1.50%apricot kernel oil 13.00% fragrance 0.40% resveratrol 1.00% ascorbicacid 5.00% xanthan 0.50% cyclopentadimethylsiloxane 5.00% sucrosemono-di-palmitostearate 3.00% methylglucose sesquistearate 3.00% stearicacid 1.00% cetyl alcohol 3.00% preservatives 0.30% sterilizeddemineralized water qs 100.00%

[0126] Composition 2: Body oil liquid petroleum jelly 47.99% apricotkernel oil 6.00% fragrance 1.00% resveratrol 0.50% ascorbic acid 3.00%cyclopentadimethylsiloxane 45.00%

[0127] Composition 3: Makeup-removing milk 2-ethylhexyl palmitate 10.50%liquid fraction of karite butter 16.50% preservatives 0.30% fragrance0.15% resveratrol 0.50% ascorbic acid 2.00% sodium hydroxide 0.04%carboxyvinyl polymer 0.20% sterilized demineralized water 69.80% mixtureof cetylstearyl glucoside 2.50% and of cetyl and stearyl alcohols

[0128] Composition 4: Hair cream beeswax 1.50% apricot kernel oil 13.00%preservatives 0.30% fragrance 0.40% triethanolamine 0.17% resveratrol1.00% ascorbic acid 5.00% beta-naphthoxyacetic acid 0.01%2,4-dichlorophenoxyacetic acid 0.01% xanthan 0.50%cyclopentadimethylsiloxane 5.00% sucrose mono-di-palmitostearate 3.00%methylglucose sesquistearate 3.00% stearic acid 1.00% cetyl alcohol3.00% sterilized demineralized water qs 100.00%

[0129] While the invention has been described in terms of variousspecific and/or preferred embodiments, the skilled artisan willappreciate that various modifications, substitutions, omissions, andchanges may be made without departing from the spirit thereof.Accordingly, it is intended that the scope of the present invention belimited solely by the scope of the following claims, includingequivalents thereof.

What is claimed is:
 1. A cosmetic/dermatological composition suited fortreating afflictions of the skin, comprising effective skinaffliction-alleviating amounts of (a) at least one hydroxystilbenecompound, in immixture with (b) at least one ascorbic acid compound. 2.The cosmetic/dermatological composition as defined by claim 1, said atleast one hydroxystilbene compound (a) having the structural formula(I):

in which n in an integer ranging from 0 to 4, inclusive, and m is aninteger ranging from 0 to 5, inclusive, or hydroxyalkyl derivativethereof.
 3. The cosmetic/dermatological composition as defined by claim2, said at least one hydroxystilbene compound (a) comprising:4′-hydroxystilbene, 2′, 4′-dihydroxystilbene, 3′,4′-dihydroxystilbene,4,4′-dihydroxystilbene, 2′, 4′, 4-trihydroxystilbene,3′,4′,4-trihydroxystilbene, 2,4,4′-trihydroxystilbene,3,4,4′-trihydroxystilbene, 3,4′, 5-trihydroxystilbene, 2′,3,4-trihydroxystilbene, 2,3′,4-trihydroxystilbene,2′,2,4′-trihydroxystilbene, 2,4,4′,5-tetrahydroxystilbene, 2′, 3,4′,5-tetrahydroxystilbene, 2,2′, 4,4′-tetrahydroxystilbene,3,3′,4′,5-tetrahydroxystilbene, 2,3′, 4,4′-tetrahydroxystilbene, 3,3′,4,4′-tetrahydroxystilbene, 3,3′,4′,5,5′-pentahydroxystilbene, 2,2′,4,4′, 6-pentahydroxystilbene, 2,3′, 4,4′, 6-pentahydroxystilbene, or2,2′, 4,4′, 6,6′-hexahydroxystilbene.
 4. The cosmetic/dermatologicalcomposition as defined by claim 3, said at least one hydroxystilbenecompound (a) comprising 3,4′, 5-trihydroxystilbene (resveratrol).
 5. Thecosmetic/dermatological composition as defined by claim 1, said at leastone ascorbic acid compound (b) comprising ascorbic acid, or salt, ester,or sugar thereof.
 6. The cosmetic/dermatological composition as definedby claim 1, formulated into a physiologically/cosmetically acceptablevehicle, diluent or carrier therefor.
 7. The cosmetic/dermatologicalcomposition as defined by claim 1, suited for topical application ontothe skin and/or mucous membranes, formulated into a topicallyapplicable, physiologically/cosmetically acceptable vehicle, diluent orcarrier therefor.
 8. The cosmetic/dermatological composition as definedby claim 6, comprising from 0.001% to 10% by weight of said at least onehydroxystilbene compound (a).
 9. The cosmetic/dermatological compositionas defined by claim 8, comprising from 0.005% to 5% by weight of said atleast one hydroxystilbene compound (a).
 10. The cosmetic/dermatologicalcomposition as defined by claim 8, comprising from 0.001% to 20% byweight of said at least one ascorbic acid compound (b).
 11. Thecosmetic/dermatological composition as defined by claim 9, comprisingfrom 0.1% to 15% by weight of said at least one ascorbic acid compound(b).
 12. The cosmetic/dermatological composition as defined by claim 11,comprising from 3% to 10% by weight of said at least one ascorbic acidcompound (b).
 13. The cosmetic/dermatological composition as defined byclaim 1, wherein the weight ratio between said least one hydroxystilbenecompound (a) and said at least one ascorbic acid compound (b) rangesfrom 5×10⁻⁵ to 10⁺⁴.
 14. A regime/regimen for stimulating theproliferation of dermal fibroblasts, comprising administering to acandidate individual in need of such treatment, a thus-effective amountof the cosmetic/dermatological composition as defined by claim
 1. 15. Aregime/regimen for preventatively/curatively treating the signs of agingof the skin, comprising administering to a candidate individual in needof such treatment, a thus-effective amount of thecosmetic/dermatological composition as defined by claim
 1. 16. Aregime/regimen for preventatively/curatively treating loose and/orwrinkled skin, comprising administering to a candidate individual inneed of such treatment, a thus-effective amount of thecosmetic/dermatological composition as defined by claim
 1. 17. Aregime/regimen for stimulating firming of the skin, comprisingadministering to a candidate individual in need of such treatment, athus-effective amount of the cosmetic/dermatological composition asdefined by claim
 1. 18. A regime/regimen for promoting the smoothness ofthe skin, comprising administering to a candidate individual in need ofsuch treatment, a thus-effective amount of the cosmetic/dermatologicalcomposition as defined by claim
 1. 19. A regime/regimen for tauteningthe skin, comprising administering to a candidate individual in need ofsuch treatment, a thus-effective amount of the cosmetic/dermatologicalcomposition as defined by claim
 1. 20. A regime/regimen for combatingthe adverse effects of menopause on the skin, comprising administeringto a candidate individual in need of such treatment, a thus-effectiveamount of the cosmetic/dermatological composition as defined by claim 1.21. A regime/regimen for combating the adverse effects of menopause oncollagen and/or dermal fibroblasts, comprising administering to acandidate individual in need of such treatment, a thus-effective amountof the cosmetic/dermatological composition as defined by claim
 1. 22.The cosmetic/dermatological composition as defined by claim 1,comprising a solution, emulsion, gel, paste, solid, dispersion, milk,lotion, serum, mousse, cream, ointment, aerosol, cleaner, makeup,deodorant, spherules, or lipid vesicles.
 23. The cosmetic/dermatologicalcomposition as defined by claim 1, further comprising an effectiveamount of at least one hydrophilic or lipophilic gelling agent,hydrophilic or lipophilic active principle, preservative, antioxidant,solvent, fragrance, vitamin, filler, UV-screening agent, colorant,chelating agent and/or odor absorber.
 24. The cosmetic/dermatologicalcomposition as defined by claim 1, further comprising an effectiveamount of at least one antibacterial agent, agent for combatingparasites, antifungal agent, antiviral agent, anti-inflammatory agent,antipruriginous agent, anaesthetic agent, keratolytic agent, agent forcombating free radicals, agent for modifying the adhesion of bacteria tothe skin and/or to mucous membranes, antiseborrhoeic agent, antidandruffagent, antiacne agent, agent which modulates cutaneous pigmentationand/or proliferation and/or differentiation, substance P, CGRP orbradykinin antagonist and/or NO-synthase inhibitor.
 25. Thecosmetic/dermatological composition as defined by claim 1, furthercomprising an effective amount of at least one active species whichpromotes the synthesis of lipids and/or promotes the proliferation ofkeratinocytes.
 26. The cosmetic/dermatological composition as defined byclaim 1, further comprising cinnamic acid and/or a plant hormone. 27.The cosmetic/dermatological composition as defined by claim 1, furthercomprising an effective amount of at least one calcium antagonist, OHradical scavenger, extract of Iridaceae or soybean, isoflavone,bacterial extract, potassium channel opener, spiroxazone, phospholipid,linoleic acid, linolenic acid, salicylic acid or derivative thereof,hydroxycarboxylic or ketocarboxylic acid or ester, lactone or saltthereof, anthralin, carotenoid, eicosatetraenoic or eicosatrienoic acidor ester or amide thereof, and/or vitamin D or derivative thereof.